Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation
Abstract Background Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which p...
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BMC
2025-06-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13287-025-04380-9 |
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| author | Jie Chen Yiwei Zhao Chongmai Zeng Guoli Tian Zhicai Feng Yang Cao |
| author_facet | Jie Chen Yiwei Zhao Chongmai Zeng Guoli Tian Zhicai Feng Yang Cao |
| author_sort | Jie Chen |
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| description | Abstract Background Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which promotes craniomaxillofacial suture growth, is a common therapeutic approach for craniofacial deformities. However, the underlying mechanisms by which mechanical forces drive suture and bone remodeling remain poorly understood, posing significant clinical challenges. Methods To investigate these mechanisms, we established a rapid maxillary expansion (RME) model in mice to widen the midpalatal suture. Single-cell RNA sequencing (scRNA-seq) was employed to identify subsets of SuSCs responsive to mechanical tension and analyze their differentiation potential under varying conditions. Further functional studies were conducted to explore the role of DALR anticodon binding domain containing 3 (Dalrd3) and its associated tRNA 3-methylcytosine (m3C) modification in SuSCs under mechanical tension. Results Our study identified a subset of SuSCs with multidirectional differentiation potential that shifted from a chondrogenic to an osteogenic trajectory in response to mechanical tension. Mechanical tension also upregulated Dalrd3 expression and its associated tRNA m3C modification in activated SuSCs. Knockdown of Dalrd3 in SuSCs significantly impaired osteogenic differentiation, proliferation, migratory capacity, and translational activity within the bone morphogenetic protein (BMP) signaling pathway. Furthermore, Dalrd3 knockdown suppressed the translational activity of inhibitor of DNA binding 3 (Id3), a key BMP-induced mediator of osteoblastogenesis. Restoring Id3 expression in Dalrd3-deficient SuSCs rescued their osteogenic, proliferative, and migratory functions. Conclusions These findings reveal a translational regulatory mechanism in SuSCs activated by mechanical tension and underscore the pivotal role of Dalrd3 in suture remodeling and bone formation. The insights provided by this study have the potential to guide targeted therapeutic strategies for optimizing distraction osteogenesis and other treatments for craniofacial deformities. |
| format | Article |
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| institution | Kabale University |
| issn | 1757-6512 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Stem Cell Research & Therapy |
| spelling | doaj-art-cd1fd885e48b4b3d9c4ff5968a1dcbff2025-08-20T03:47:24ZengBMCStem Cell Research & Therapy1757-65122025-06-0116112010.1186/s13287-025-04380-9Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translationJie Chen0Yiwei Zhao1Chongmai Zeng2Guoli Tian3Zhicai Feng4Yang Cao5Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityHospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen UniversityAbstract Background Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which promotes craniomaxillofacial suture growth, is a common therapeutic approach for craniofacial deformities. However, the underlying mechanisms by which mechanical forces drive suture and bone remodeling remain poorly understood, posing significant clinical challenges. Methods To investigate these mechanisms, we established a rapid maxillary expansion (RME) model in mice to widen the midpalatal suture. Single-cell RNA sequencing (scRNA-seq) was employed to identify subsets of SuSCs responsive to mechanical tension and analyze their differentiation potential under varying conditions. Further functional studies were conducted to explore the role of DALR anticodon binding domain containing 3 (Dalrd3) and its associated tRNA 3-methylcytosine (m3C) modification in SuSCs under mechanical tension. Results Our study identified a subset of SuSCs with multidirectional differentiation potential that shifted from a chondrogenic to an osteogenic trajectory in response to mechanical tension. Mechanical tension also upregulated Dalrd3 expression and its associated tRNA m3C modification in activated SuSCs. Knockdown of Dalrd3 in SuSCs significantly impaired osteogenic differentiation, proliferation, migratory capacity, and translational activity within the bone morphogenetic protein (BMP) signaling pathway. Furthermore, Dalrd3 knockdown suppressed the translational activity of inhibitor of DNA binding 3 (Id3), a key BMP-induced mediator of osteoblastogenesis. Restoring Id3 expression in Dalrd3-deficient SuSCs rescued their osteogenic, proliferative, and migratory functions. Conclusions These findings reveal a translational regulatory mechanism in SuSCs activated by mechanical tension and underscore the pivotal role of Dalrd3 in suture remodeling and bone formation. The insights provided by this study have the potential to guide targeted therapeutic strategies for optimizing distraction osteogenesis and other treatments for craniofacial deformities.https://doi.org/10.1186/s13287-025-04380-9Bone suture stem cellsMechanical tensionDalrd3OsteogenesisTRNA m3 C modification |
| spellingShingle | Jie Chen Yiwei Zhao Chongmai Zeng Guoli Tian Zhicai Feng Yang Cao Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation Stem Cell Research & Therapy Bone suture stem cells Mechanical tension Dalrd3 Osteogenesis TRNA m3 C modification |
| title | Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation |
| title_full | Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation |
| title_fullStr | Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation |
| title_full_unstemmed | Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation |
| title_short | Mechanical tension-induced Dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating Id3 translation |
| title_sort | mechanical tension induced dalrd3 elevation enhances osteogenic differentiation of bone suture stem cells by upregulating id3 translation |
| topic | Bone suture stem cells Mechanical tension Dalrd3 Osteogenesis TRNA m3 C modification |
| url | https://doi.org/10.1186/s13287-025-04380-9 |
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